The overall goal of this application is to support the education and clinical research of the investigator leading to an independent career in patient-oriented research focused on HIV-related kidney disease. With the career development award and a program of didactic and scientific training, the goals will be achieved by: 1) receiving direct mentorship in study methods, statistical analysis, scientific communication and manuscript preparation 2) obtaining formal instruction in the Graduate Training Program in Clinical Investigation and advanced courses in cohort design/ statistical analysis and genetic epidemiology and 3) implementing the research proposal with guidance and input from mentors and collaborators in the supportive environment offered by the Johns Hopkins Schools of Medicine and Public Health, and the Welch Center for Prevention, Epidemiology and Clinical Research. Survival of HIV-infected individuals has improved significantly with highly active antiretroviral therapy (HAART); consequently, chronic illnesses such as kidney disease are of increasing concern. The overall aim of the proposal is to quantify the burden of chronic kidney disease (CKD) in HIV-infected individuals using serum creatinine and cystatin C and to investigate whether HIV- and host-related factors are involved in the development and progression of CKD in HIV-positive individuals. This proposal will use two unique study populations: 1) a large, racially diverse population of HIV-positive individuals with extended follow-up from the Multicenter AIDS Cohort Study (MACS) and the Womens' Interagency HIV Study (WIHS) cohorts; and 2) a clinic-based study population of HIV-positive individuals recruited through the Johns Hopkins HIV/AIDS Service. This proposal will provide: 1) the current epidemiology of HIV-related CKD in the U.S. and its impact on mortality; 2) a comparison of the prevalence of CKD based on cystatin C versus serum creatinine estimates of kidney function; 3) an investigation of the risk of CKD development and progression related to HAART and HIV disease stage; and 4) a validation of the association of MYH9 with CKD progression and specific renal histopathologic findings. PUBLIC HEALTH RELEVANCE: This proposal will have important implications in screening and identifying CKD in this high risk population. It will determine the impact of CKD in the natural history of HIV infection and determine risk factors for CKD during the HAART era. It will yield a potential mechanism for HIV-related CKD which may ultimately lead to the development of diagnostic and prognostic markers for HIV-related CKD.